This grant proposes to examine the pharmacokinetics of methylphenidate and its metabolites in children, adults and animals. Established analytical procedures will be used to related therapeutic effectiveness in the treatment of "Attentional deficit disorder with hyperkinesis" to blood content of methylphenidate and its metabolites. These investigations will be made in children and adults and will allow conclusions whether the lack of therapeutic response to methylphenidate in some patients can be attributed to differences in pharmacokinetic profile. Other studies will be undertaken to relate variable responses to methylphenidate to changes in blood levels and to examine the role of food ingestion in the unpredictable to changes in blood levels and to examine the role of food ingestion in the unpredictable therapeutic effects noted in some patients. Preclinical studies will complement clinical investigations by defining active metabolites and performing pharmacokinetic investigations in animals. These latter experiments will permit choice of metabolites to be studied and enhance interpretation of clinical data. The present investigations are intended to establish a more rational pharmacological basis for making practical clinical decisions concerning the use of methylphenidate in the treatment of children and adults with behavioral disorders.